Analysis of the yield of phase II combination therapy trials in medical oncology.
Analysis of the yield of phase II combination therapy trials in medical oncology.
复制标题
DOI：
10.1158/1078-0432.ccr-10-0669
复制
发表时间：
2010-11-01
期刊：
影响因子：
--
通讯作者：
Ratain MJ
中科院分区：
文献类型：
--
作者：
Maitland ML;Hudoba C;Snider KL;Ratain MJ
II期临床研究筛选改善患者护理的治疗方案，但筛选联合方案尤其具有挑战性。我们假设，在联合治疗研究中，单组试验的公认缺陷可能会被放大，导致许多报道的阳性II期试验，但很少有导致实践改变的III期试验。我们检索了medline，确定了2001年和2002年发表的363个联合化疗临床试验。根据对摘要和文本的标准化审查，将研究评定为阳性、阴性或不确定。检索Web of Science Index（Thomson路透社，NY，NY），检索2003年至2007年10月期间发表的所有文章，这些文章至少引用了这363项已发表试验中的1项。在363项已发表的II期联合化疗试验中，262项（0.72）被宣布为阳性。在3760篇独特的后续引用论文中，20篇报告了与源论文相同疾病的相同组合的随机III期试验，其中10篇导致了护理标准的提高。根据这些数据估计，已发表的阳性II期联合化疗试验将导致后续试验在5年内证明标准治疗改善的可能性为0.038 [95%置信区间-0.016，0.064]。尽管有超过16，000名受试者参与，但根据2001-02年标准进行的联合化疗II期试验的贡献值较低。未来的联合方案II期研究需要更好的方法来筛选最有可能提高护理标准的治疗方法。
Phase II clinical studies screen for treatment regimens that improve patient care, but screening combination regimens is especially challenging. We hypothesized that recognized flaws of single arm trials could be magnified in combination treatment studies, leading to many reported positive phase II trials but a low fraction resulting practice-changing phase III trials. We searched medline and identified 363 combination chemotherapy clinical trials published in 2001 and 2002. Studies were rated as positive, negative, or inconclusive based on standardized review of abstract and text. The Web of Science Index (Thomson Reuters, NY, NY) was searched for all articles published between 2003 and October 2007 that cited at least one of these 363 published trials. Of 363 published phase II combination chemotherapy trials, 262 (0.72) were declared to be positive. Among 3760 unique subsequent citing papers, 20 reported randomized phase III trials of the same combination in the same disease as the source paper, and 10 of these resulted in improved standards of care. Estimating from these data, the likelihood that a published, positive phase II combination chemotherapy trial will result in a subsequent trial demonstrating an improvement in standard of care within five years was 0.038 [95% confidence interval- 0.016, 0.064]. The contributory value of combination chemotherapy phase II trials performed by 2001-02 standards is low despite the participation of more than 16,000 subjects. Future phase II studies of combination regimens require better methods to screen for treatments most likely to improve standards of care.